Fixed-dose Combination Of Amlodipine Research Articles

Effectiveness and Safety of the Telmisartan and Amlodipine Fixed-dose Combination in Managing Hypertension among Indian Patients (TACT India Study): Rationale and Study Design.

Background: The prevalence of hypertension is on the rise, with approximately 200 million individuals affected by this condition in India. Epidemiological studies suggest that one in every three adults in India has hypertension. Fixed-dose combinations (FDCs) present a potential strategy to address the challenge of effective blood pressure control. They are now recommended for the initiation in most hypertensive patients by the guidelines. However, studies evaluating the safety and effectiveness of FDCs in large Indian populations with hypertension are few. Aim: The aim of this real-world study is to evaluate the safety and effectiveness of the fixed-dose combination of telmisartan and amlodipine in managing hypertension in Indian patients. Materials and methods: This prospective, multicenter, observational, real-world evidence study is designed to enroll 10,000 eligible participants from 1,000 study sites across India. Adult patients with newly diagnosed or uncontrolled hypertension on monotherapy would be eligible for enrollment in the study. The study participants would be administered the study treatment per the treating physician's routine clinical practice and followed up after 8 weeks. The primary endpoint is to measure the change in systolic blood pressure (SBP) from baseline to week 8, while secondary endpoints include determining the percentage of patients who reach their blood pressure targets., description of demographic characteristics of the Indian hypertensive population, and reporting of safety outcomes. Conclusion: The TACT India study will provide longitudinal, real-world data on the effectiveness and safety of telmisartan and amlodipine FDC among a large cohort of the Indian population with hypertension.

Clinical Benefit of Fixed-Dose Combination of Amlodipine and Potent Atorvastatin in Patients With Concomitant Hypertension and Hypercholesterolemia.

Hypertension and hypercholesterolemia are important risk factors for cardiovascular disease, and treatment with fixed-dose combination (FDC) regimens is recommended by current guidelines. However, the clinical outcomes of different FDC dosages remain unknown. This study aimed to examine the clinical outcomes of FDC regimens and the free combination of amlodipine and atorvastatin at different dosages. Patients with concurrent hypertension and hypercholesterolemia treated daily with an FDC of 5 mg amlodipine and 10 mg atorvastatin (5/10 fixed group), and FDC of 5 mg amlodipine and 20 mg atorvastatin (5/20 fixed group), or free combination of 5 mg amlodipine and 20 mg atorvastatin (5/20 free group) were identified from the National Health Insurance Research Database of Taiwan. The primary outcome was the composite cardiovascular outcomes, including cardiovascular death, acute myocardial infarction, stroke, and coronary intervention. A total of 9095 patients were eligible for inclusion. The incidence of primary outcome per 1000 person-years was 16.6 in the 5/10 fixed group, 12.6 in the 5/20 fixed group, and 16.5 in the 5/20 free group (5/20 fixed versus 5/20 free: hazard ratio [HR], 0.76 [95% CI, 0.64-0.91]; 5/20 fixed versus 5/10 fixed: HR, 0.76 [95% CI, 0.63-0.90]). Among patients with concomitant hypertension and hypercholesterolemia, treatment with an FDC of amlodipine and high-dose atorvastatin led to a lower risk of a composite of cardiovascular outcomes than treatment with the free combination or a similar FDC with a lower dose of atorvastatin.

Rationale and Study Design of Evaluation of Effectiveness and Safety of Telmisartan and Amlodipine Fixed Dose Combination in Indian Hypertensive Patients (TACT-India): A Prospective, Longitudinal, Multicentre, Observational Study

Rationale and Study Design of Evaluation of Effectiveness and Safety of Telmisartan and Amlodipine Fixed Dose Combination in Indian Hypertensive Patients (TACT-India): A Prospective, Longitudinal, Multicentre, Observational Study

Beneficial Effects of Fixed-Dose Combination of Amlodipine and Atorvastatin in Patients with Concomitant Hypertension and Hypercholesterolemia: A Multi-Institutional Cohort Study.

Blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) are important risk factors for cardiovascular (CV) diseases. Although treating these factors simultaneously is recommended by current guidelines, only short-term clinical results are available. To examine the longer-term efficacy and safety of fixed-dose combination (FDC) versus free combination of amlodipine and atorvastatin in patients with concomitant hypertension and hypercholesterolemia. Patients with hypertension and hypercholesterolemia were stratified into three groups [FDC of amlodipine 5 mg/atorvastatin 10 mg (Fixed 5/10), FDC of amlodipine 5 mg/atorvastatin 20 mg (Fixed 5/20), and free combination of amlodipine 5 mg/atorvastatin 10 mg (Free 5/10)]. After inverse probability of treatment weighting, the composite CV outcome, liver function, BP, LDL-C and glycated hemoglobin (HbA1c) changes were compared. A total of 1,788 patients were eligible for analysis, and the mean follow-up period was 1.7 year. There was no significant difference in the composite CV outcome among the three groups (Fixed 5/10 6.1%, Fixed 5/20 6.3% and Free 5/10 6.0%). The LDL-C level was significantly reduced in the Fixed 5/20 group (-35.7 mg/dL) compared to the Fixed 5/10 (-23.6 mg/dL) and Free 5/10 (-10.3 mg/dL) groups (p = 0.001 and < 0.001, respectively). The changes in HbA1c were similar among the three groups. FDC of amlodipine and atorvastatin, especially the regimen with a higher dosage of statins, significantly reduced the mid-term LDL-C level compared to a free combination in patients with concomitant hypertension and hypercholesterolemia. Blood sugar level was not significantly changed by this aggressive treatment strategy.

История комбинированной защиты: 25 лет применения в клинической практике комбинированного препарата, содержащего амлодипин и бисопролол

The paper discusses the role of Concor AM, the fixed-dose combination of amlodipine and bisoprolol, which has been used in clinical practice for treatment of patients with cardiovascular diseases for 25 years. The data are provided on the benefits of using Concor AM in treatment of patients with arterial hypertension and coronary artery disease. Evidence is discussed that illustrated the advantages of using such fixed-dose combination compared to the combination use of amlodipine and bisoprolol in the form of the so-called free combination. The evidence also includes the results of the recently completed randomized clinical trial that involved comparative analysis of the use of Concor AM and irbesartan monotherapy as part of the initial strategy for antihypertensive therapy. The role of each component of Concor AM in modern therapy for patients with cardiovascular diseases is considered.

Perindopril Arginine, Indapamide, and Amlodipine Fixed Dose Combination Induced Gingival Overgrowth: Two Cases with Specific Clinical Presentation

Drug induced gingival overgrowth (DIGO) is a frequent adverse effect of systemic medications. Amlodipine, although accepted as a safe antihypertensive drug due to its longer duration of action with lower dose and fewer adverse reactions compared to other antihypertensive agents, is among the causative drugs. As the aetiology of hypertension is multifactorial, a fixed dose combination containing amlodipine and other antihypertensive agents is currently preferred by physicians as a new treatment approach. The aim of this article is to report two cases of perindopril arginine, indapamide, and amlodipine fixed dose combination induced gingival overgrowth with an emphasis on the specific clinical presentation. Intraoral examination revealed poor oral hygiene, excessive dental plaque accumulation, and erythematous, oedematous, lobulated, enlarged marginal and interdental gingivae prone to bleeding. It was noteworthy that a red band appearance was present on the enlarged labial marginal gingivae in the patients. One month after the drug substitution, proper oral hygiene education and plaque control, and non-surgical periodontal treatment, a marked regression in DIGO and accompanying inflammatory symptoms were observed. Medical and dental practitioners should be aware that antihypertensive drugs used alone or in combination with other agents have the potential to cause gingival overgrowth.

Pharmacokinetics of a Fixed-Dose Combination of Amlodipine/Losartan and Chlorthalidone Compared to Concurrent Administration of the Separate Components.

Hypertension is more effectively treated with coadministration of 2 or more antihypertensive drugs than with high-dose monotherapy. Therefore, calcium channel blockers, angiotensin II receptor blockers, and thiazides are coadministered to treat hypertension. The objective of this study was to compare the pharmacokinetic (PK) profiles of HCP1401, a fixed-dose combination of amlodipine 5 mg, losartan 100 mg, and chlorthalidone 25 mg, with the separate components (loose combination) of amlodipine/losartan 5/100 mg and chlorthalidone 25 mg. A randomized, open-label, single-dose, 2-way crossover study was conducted. Blood samples for amlodipine and chlorthalidone were collected for up to 144 hours after dosing, whereas those for losartan were collected up to 48 hours after dosing. The PK parameters of these drugs were calculated using a noncompartmental method. Sixty subjects completed the study. The geometric mean ratios and 90% confidence intervals of maximum plasma concentration and area under the concentration-time curve to the last measurable point for amlodipine, losartan, and chlorthalidone were within the conventional bioequivalence range of 0.80 to 1.25. There were no clinically significant changes in safety assessments, and the treatments were well tolerated. The PK characteristics and tolerability profiles of a single oral FDC of amlodipine, losartan, and chlorthalidone were equivalent to those of individual tablets in a loose combination.

Fixed-dose combination amlodipine–celecoxib for treatment of hypertension and osteoarthritis pain: an up-to-date evaluation

ABSTRACT Introduction: A fixed-dose combination of amlodipine and celecoxib, branded in the USA as Consensi®, was recently granted a US Food and Drug Administration (FDA)-approved indication for treatment of comorbid hypertension and osteoarthritis. Areas covered: A PubMed and Medline search was conducted for clinical trials published through December 2020 in the English language using keywords amlodipine, celecoxib, combination product, consensi, hypertension, osteoarthritis, and pill burden. Although no clinical trials have been published in the peer-reviewed literature, results from two phase 3 clinical trials reported to ClinicalTrials.gov suggest that amlodipine–celecoxib has similar short-term efficacy compared with amlodipine alone in reducing blood pressure and a comparable adverse event profile to the individual components administered alone. Expert opinion: Despite the pill burden reduction and a body of evidence supporting the efficacy and safety of the individual drugs, the role of amlodipine–celecoxib in the management of patients with hypertension–osteoarthritis remains in question. This is in no small part because the combination product is very costly relative to the generic components, provides limited flexibility for dose-adjustment, and lacks long-term data on safety and efficacy.

Psychological continuum of elderly hypertensive patients with metabolic syndrome receiving chronotherapy with a fixed-dose combination of amlodipine, lisinopril and rosuvastatin

Aim. To study the psychological continuum of elderly hypertensive patients with metabolic syndrome (MS) receiving chronotherapy with a fixed-dose combination of amlodipine, lisinopril and rosuvastatin.Material and methods. In a clinical setting, 63 hypertensive patients with MS aged 60-74 years (experimental group) received chronotherapy with fixed-dose combination of amlodipine, lisinopril and rosuvastatin (Ekvamer®) at a dose of 5/10/10 mg in the evening (8 pm). The control group of hypertensive patients with MS aged 60-74 years old (n=58) received Ekvamer® in the morning (conventional therapy) at the same dosage.Results. With fixed-dose combination of amlodipine, lisinopril and rosuvastatin, the severity of psychological continuum abnormalities significantly decreases after 1 year in the chronotherapy regimen (evening intake) than with morning intake with an equivalent dosage of 5/10/10 mg per day in both cases. The dynamics of cognitive impairments in hypertensive patients aged 60-74 years with MS using chronotherapy regimen is characterized by a significant increase in the mean MMSE score from the initial 17,8±0,3 to 23,5±0,4 points (p±0,001) vs 16,9±0,3 to 20,4±0,4 points (p&lt;0,001) when taking the drug in the morning. Situational anxiety decreased from 40,0±2,2 to 30,6±1,8 points (p&lt;0,05) vs 40,8±2,5 to 33,5±1,9 points (p&lt;0,05), personal anxiety from 48,8±2,0 to 26,4±1,9 (p&lt;0,001) vs from 44,9±1,9 to 30,7±1,7 (p&lt;0,01) points, respectively. Depressive disorders slightly decreased with chronotherapy (14,1%) vs 7,7% than with the conventional scheme, but despite this, they corresponded to depressive spectrum disorders in both groups.Conclusion. The results obtained indicate a greater efficiency of chronotherapy than the conventional use of fixed-dose combination of amlodipine, lisinopril and rosuvastatin in hypertensive patients with MS.

Increment of the effectiveness of treating hypertension and dyslipidemia using a triple fixed-dose combination and the vascular age concept

Aim . To study the efficacy, safety and effect on vascular age of free-equivalent and fixed-dose combinations of amlodipine, a renin-angiotensin-aldosterone system blockers and rosuvastatin in patients with high and very high cardiovascular risk with uncontrolled hypertension and concomitant dyslipidemia. Material and methods . This open-label case series study included 148 men and women (mean age 60,63±8,16 years). The patients were randomly divided into 2 groups: group 1 (n=76) received a triple fixed-dose combination of amlodipine, lisinopril, rosuvastatin; group 2 (n=72) received a dual free-equivalent antihypertensive combination (amlodipine/losartan) and rosuvastatin. The doses were selected by the attending physician and were not regulated by the researchers. The study included an assessment of blood pressure, lipid profile (total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, triglycerides), biochemical profile, ASCORE value, medication adherence, changes in the augmentation index (AI) at baseline and after 6 months of therapy (first and second visits, respectively). The results were considered significant at p&lt;0,05. Results . After 6 months of therapy, significant intragroup differences were noted in comparison with the baseline values. In group 1, the levels of TC (p=0,002), LDL-C (p=0,001), ASCORE value (p=0,01), and vascular age (p=0,01) significantly decreased; in group 2 — TC (p=0,03), LDL-C (p=0,005). In the group of triple fixed-dose therapy, the values of AI (p=0,04), TC (p=0,012), LDL-C (p=0,024), ASCORE value (p=0,02) and vascular age (p=0,01) were significantly lower than in the free-equivalent group. Conclusion . The fixed-dose combination of amlodipine, lisinopril and rosuvastatin, is more effective and equally safe relative to the free-equivalent combination of amlodipine/losartan and rosuvastatin, not only in terms of effect on LDL-C and AI, but also on vascular age parameters calculated using the ASCORE scale. This can serve as an additional motivating factor for patients to receive therapy.

Bioequivalence of a medicinal product PERINDOPRES A (perindopril and amlodipine fixed-dose combination) to the original medicinal product Bi-PRESTARIUM®: the results of a randomized crossover clinical trial in healthy volunteers

Bioequivalence of a medicinal product PERINDOPRES A (perindopril and amlodipine fixed-dose combination) to the original medicinal product Bi-PRESTARIUM®: the results of a randomized crossover clinical trial in healthy volunteers

Medical adherence in hypertensive patients treated by triple fixed-dose combination of amlodipine / indapamide / perindopril arginine (results of the Study DOKAZATEL’STVO)

Objective. To estimate changes in medication adherence in patients treated with fixed-dose combination of amlodipine / indapamide / perindopril arginine included in DOKAZATEL’STVO observational study.Design and methods. Effects of the fixed-dose combination of amlodipine / indapamide / perindopril arginine on medication adherence were assessed in 1554 patients who filled in the questionnaire at baseline and at the last visit. Primary outcomes of the study included the change in the office and ambulatory (home blood pressure (BP) monitoring) systolic and diastolic BP from baseline to 3 months and rate of the achievement of target BP &lt; 140/90 mmHg after 3-month treatment. Adherence was assessed by special questionnaire.Results. The fixed-dose combination of amlodipine / indapamide / perindopril arginine resulted in the decrease in systolic BP by 39.5 mmHg and diastolic BP by 18.8 mmHg after 3 months. Target office BP &lt; 140/90 mmHg was achieved in 87 %. High adherence at baseline was observed in 7,1 % patients, after 3 months of treatment — in 38,3 % (p &lt; 0,001). Mean adherence score increased from 2,9 ± 1,6 to 5,0 ± 1,1 (p &lt; 0,001). Study drug intake was associated with increase in motivation and awareness from 38 % to 95,4 % and from 19,8 % to 67,3 %, respectively (p &lt; 0,001 for trend).Conclusions. The administration of the fixed-dose combination of amlodipine / indapamide / perindopril arginine was associated with well tolerated BP decrease and significant increase in medication adherence and motivation even in the absence of specific targeted interventions.

Biochemical, Pharmacological, and Therapeutic Effects of Triple Antihypertensive Therapy with Amlodipine, Valsartan and Hydrochlorothiazide in Elderly Hypertensive Patients with Calcium Phosphate Nephrolithiasis

Antihypertensives are widely prescribed in the geriatric population and could influence kidney stone risk but many aspects are still unknown. Thiazides are used to control lithogenic factors and recurrences in patients with calcium lithiasis. The aim of our study was to evaluate the relationship between essential arterial hypertension and stone disease, by studying the pharmaco-therapeutic effects of a fixed-dose combination of amlodipine + valsartan + hydrochlorothiazide (Aml + Val + HCTZ) 10/320/25 mg, on the urinary stone risk in a study group of hypertensive geriatric patients. A longitudinal, randomized, three years follow-up clinical and experimental study was conducted during June 1, 2014 - July 31, 2017. A number of 60 eligible geriatric patients, treated only with a fixed-dose combination of Aml + Val + HCTZ 10/320/25 mg, as a single-tablet, were enrolled in the study. All the patients were stone formers, with more than three episodes of crystalluria in the last two years. The patient�s age ranged between 55 and 65 years. Exclusion criteria: patients with heart failure, kidney chronic diseases, use of drugs known to affect renal function, patients with multi-morbidities. All patients had similar blood pressure values, and tension was well controlled throughout the whole study period. In the elderly patients, the treatment with 25 mg/day of hydrochlorothiazide (from the combination of Aml + Val + HCTZ 10/320/25 mg) has a beneficial and prolonged efficacy in treatment of recurrences in patients with calcium oxalate and phosphate lithiasis Our study reveals that in the elderly patients with hypertension and nephrolithiasis as a comorbidity, thiazides - 25 mg/day of hydrochlorothiazide (from the combination of Aml + Val + HCTZ 10/320/25 mg) has a beneficial effect in order to control lithogenic factors and recurrences in patients with calcium phosphate lithiasis.

Does a fixed-dose combination of amlodipine and atorvastatin improve persistence with therapy in the Australian population?

Aim: To compare persistence in people who initiate the combination of amlodipine and statin as a fixed-dose combination (FDC) or separate pill combination (SePC), and assess the impact of prior medicine exposure on this outcome.Method: Prescription dispensing data from a national administrative dataset was used to identify patients initiating FDCs or SePCs of amlodipine and statin between April and September 2013. Each cohort was stratified according to dispensing of calcium channel blockers (CCBs) or statins in the prior 12 months. Time to cessation of combination therapy (persistence) was analyzed over 12 months using Kaplan Meyer survival analysis and Cox proportional hazards (PH) models. Patient factors associated with length of treatment were identified using Cox PH modeling.Results: Of 26,000 people who initiated combination amlodipine and statin, the majority initiated SePCs (77%). The unadjusted cessation rates at 12 months were SePC 40% and FDC 44%. Following adjustment for patient factors, the risk of ceasing combination therapy was higher in those taking the SePC versus FDC, hazard ratio (95% CI): 1.15 (1.11, 1.21). Patients naïve to both therapies had double the cessation rate compared to those who had at least one prior dispensing of a statin. Factors positively associated with persistence were prior use of other antihypertensive drugs and reaching the medicine subsidy safety-net: factors that were more common in users of SePC amlodipine and statin.Conclusion: In this study we found a lower risk (15%) of ceasing combination therapy when people initiate amlodipine and statin in the form of a FDC. While this outcome supports findings in other countries that FDCs improve persistence with combination therapy, prior experience with component or similar medicines has a larger impact on persistence regardless of formulation initiated.

Az atorvastatin/amlodipin fix kombináció versus az atorvastatinterápia a terápiahűség tükrében

Hypertension and dyslipidemia are modifiable cardiovascular risk factors. In Hungary hypertension and dyslipidemia are quite frequent conditions. The patients' adherence is very important factor to reach the targets. The aim of the authors was to investigate the one-year persistence of the atorvastatin therapy and atorvastatin and amlodipine fixed dose combination. National Health Insurance Found prescriptions database of Hungary on pharmacy claims between October 1, 2012 and September 30, 2013 was analyzed. The authors identified patients who filled prescriptions for atorvastatin and amlodipine fixed dose combination and atorvastatin prescribed for the first time. Patients did not receive similar drugs for one year before the study. To model the persistence, the apparatus of survival analysis was used, where "survival" was the time to abandon the medication. As it was available to month precision, discrete time survival analysis was applied: a generalized linear model was estimated with complementary log-log link function with the kind of drug being the only explanatory variable. During the trial period, atorvastatin and atorvastatin plus amlodipine fixed dose combination was started in 192,579 and 24,433 patients, respectively. One year persistence rate in patients with atorvastatin and amlodipine fixed dose combination was 43%, and 21% in patients with atorvastatin therapy. The 360-days-restricted study period, the mean duration of persistence was 221.4 (SE: 0.894) days in patients on atorvastatin and amlodipine fixed dose combination and 153.0 days (SE: 0.297) in those on atorvastatin regimen. The hazard of discontinuation was almost twofold higher during treatment with atorvastatin therapy compared with the use of the atorvastatin and amlodipine fixed dose combination (hazard ratio = 1.85, p<0.0001). There is a significant difference between the one-year persistence of atorvastatin therapy and atorvastatin plus amlodipine fixed dose combination. The result demonstrate that atorvastatin and amlodipine fixed dose combination is favourable to reach double goals on blood pressure and LDL-cholesterol.

Ramipril plus amlodipine and lisinopril plus amlodipine fixed dose combinations and patient's adherence

Patient's adherence has a great significance to reach target blood pressure values. The risk of cardiovascular adverse events decreases when patients are on target blood pressure. The aim of the authors was to investigate the one-year persistence of the ramipril/amlodipine and lisinopril/amlodipine fixed dose combination in hypertensive patients. National Health Insurance Found prescriptions database of Hungary on pharmacy-claims between October 1, 2012 and September 30, 2013 was analyzed. The authors identified patients who filled prescriptions for fixed dose combinations of ramipril and amlodipine, and lisinopril and amlodipine prescribed for the first time, for the therapeutic indication of hypertension. Patients have not received antihypertensive therapy with similar active substances during one year before the study. To model the persistence, the apparatus of survival analysis was used, where "survival" was the time to abandon the medication. As it was available to month precision, discrete time survival analysis was applied: a generalized linear model was estimated with complementary log-log link function with the kind of drug being the only explanatory variable. During the study period, fixed dose combination antihypertensive therapy with ramipril plus amlodipine and lisinopril plus amlodipine was started in 10,449 and 20,276 patients, respectively. One-year persistence rate in patients taking ramipril and amlodipine as a fixed dose combination was 54%, whereas 36% in those on the fixed lisinopril and amlodipine combination. Considering only the 360-day study period, the mean duration of persistence was 271 days in patients on the ramipril based and 211 days on lisinopril based fixed dose combination. Analyzing persistence on treatment with these combinations showed that the actual rate of discontinuation was about twice higher during treatment with the lisinopril and amlodipine fixed dose combination compared with the use of the ramipril and amlodipine fixed dose combination (hazard ratio = 1.79, p<0.001). There is a significant difference between the one-year persistence of ramipril plus amlodipine and lisinopril plus amlodipine fixed dose combination in patients with hypertension. The result demonstrated that ramipril and amlodipine fixed dose combination has a favourable patients' adherence as compared to lisinopril and amlodipine fixed dose combination.

Влияние фиксированной комбинации амлодипина и бисопролола на сосудистую эластичность у пациентов с артериальной гипертензией

Влияние фиксированной комбинации амлодипина и бисопролола на сосудистую эластичность у пациентов с артериальной гипертензией

Safety and tolerability of fixed antihypertensive combinations in blood pressure control: focus on olmesartan medoxomil and amlodipine combination.

Hypertension is a major health problem worldwide and remains underdiagnosed and undertreated. Although public awareness and control of hypertension have improved over the last decade, only one-third of hypertensive patients achieve the rather conservative blood pressure (BP) goal of <140/90 mmHg. Most hypertensive patients require more than one drug for optimum BP control. Expert panels recommend use of combination therapy with two or more medications for Stage 2 and higher hypertension and in high-risk patients. However, the use of multiple drugs reduces patient compliance. Fixed-dose combination therapy helps improve patient compliance and thus achieve the target BP. Dose titration of the individual constituent drugs is recommended before switching to an equivalent fixed-dose combination. Randomized, controlled trials have shown that the fixed-dose combination of amlodipine–olmesartan medoxomil is more effective in lowering BP than monotherapy with either of these agents, with a similar side effect profile.

Efficacy and Tolerability of a Fixed-Dose Combination of Metoprolol Extended Release/Amlodipine in Patients with Mild-to-Moderate Hypertension

Epidemiological studies and clinical trials have shown that prevention of cardiovascular disease, the ultimate goal of hypertension treatment, requires a sufficient reduction in blood pressure. The primary objective of this study was to compare the mean decrease in systolic (SBP) and diastolic (DBP) blood pressure between metoprolol extended release (XL)/amlodipine fixed-dose combination and losartan plus amlodipine combination in patients with mild-to-moderate essential hypertension. The secondary objectives of this study were to compare the proportion of responders in the two treatment groups and to evaluate the tolerability of the study medications. This was a randomized, parallel-group, multicentre comparative study conducted at the outpatient departments of three teaching hospitals in India. Patients with mild-to-moderate hypertension (defined as DBP 90-109 mmHg) aged between 18 and 75 years were enrolled in this study and followed up for 12 weeks. Response to study treatments was evaluated in terms of mean decrease in SBP and DBP and the response rate (reduction to SBP <140 mmHg and DBP <90 mmHg). Out of 152 patients who underwent a 1-week placebo washout, 148 eligible patients were randomized to receive either metoprolol XL 25 mg/amlodipine 2.5 mg fixed-dose combination (76 patients) or losartan 25 mg plus amlodipine 2.5 mg (72 patients). The two treatment groups were similar with respect to demographic and baseline characteristics. Non-responders after 4 weeks of therapy were escalated to metoprolol XL 50 mg/amlodipine 5 mg fixed-dose combination or losartan 50 mg plus amlodipine 5 mg, respectively. The study was completed by 66 patients in each group, of whom 43 patients in each group responded to the starting doses. After 4 weeks' therapy, both treatments were associated with significant decreases in SBP and DBP from baseline (p < 0.001) and were comparable with respect to mean decrease in SBP (p = 0.304), mean decrease in DBP (p = 0.630) and response rate (p = 1.0). Also, both the step-up therapies were comparable with respect to mean decrease in SBP (p = 0.484), mean decrease in DBP (p = 0.650) and response rate (p = 0.134) at week 12. Both treatments were well tolerated in the studied population. Metoprolol XL/amlodipine fixed-dose combination was found to be as effective and well tolerated as losartan plus amlodipine in the treatment of essential hypertension.

Treatment of essential hypertension with calcium channel blockers: what is the place of lercanidipine?

In all actual clinical guidelines, dihydropyridine calcium channel blockers (CCBs) belong to the recommended first line antihypertensive drugs to treat essential hypertension. Several recent large clinical trials have confirmed their efficacy not only in lowering blood pressure but also in reducing cardiovascular morbidity and mortality in hypertensive patients with a normal or high cardiovascular risk profile. In clinical trials such as ALLHAT, VALUE or ASCOT, an amlodipine-based therapy was at least as effective, when not slightly superior, in lowering blood pressure and sometimes more effective in preventing target organ damages than blood pressure lowering strategies based on the use of diuretics, beta-blockers and blockers of the renin-angiotensin system. One of the main clinical side effects of the first and second generation CCBs including amlodipine is the development of peripheral edema. The incidence of leg edema can be markedly reduced by combining the CCB with a blocker of the renin-angiotensin system. This strategy has now led to the development of several fixed-dose combinations of amlodipine and angiotensin II receptor antagonists. Another alternative to lower the incidence of edema is to use CCBs of the third generation such as lercanidipine. Indeed, although no major clinical trials have been conducted with this compound, clinical studies have shown that lercanidipine and amlodipine have a comparable antihypertensive efficacy but with significantly less peripheral edema in patients receiving lercanidipine. In some countries, lercanidipine is now available in a single-pill association with an ACE inhibitor thereby further improving its efficacy and tolerability profile.